Characterization of inducible cyclooxygenase in rat brain

Abstract

Considerable debate exists regarding the cellular source of prostaglandins in the mammalian central nervous system (CNS). At least two forms of prostaglandin endoperoxide synthase, or cyclooxygenase (COX), the principal enzyme in the biosynthesis of these mediators, are known to exist. Both forms have been identified in the CNS, but only the distribution of COX 1 has been mapped in detail. In this study, we used Western blot analysis and immunohistochemistry to describe the biochemical characterization and anatomical distribution of the second, mitogen-inducible form of this enzyme, COX 2 in the rat brain. COX 2-like immunoreactive (COX 2-ir) staining occurred in dendrites and cell bodies of neurons, structures that are typically postsynaptic. It was noted in distinct portions of specific cortical laminae and subcortical nuclei. The distribution in the CNS was quite different from COX 1. COX 2-ir neurons were primarily observed in the cortex and allocortical structures, such as the hippocampal formation and amygdala. Within the amygdala, neurons were primarily observed in the caudal and posterior part of the deep and cortical nuclei. In the diencephalon, COX 2-ir cells were also observed in the paraventricular nucleus of the hypothalamus and in the nuclei of the anteroventral region surrounding the third ventricle, including the vascular organ of the lamina terminalis. COX 2-ir neurons were also observed in the subparafascicular nucleus, the medial zona incerta, and pretectal area. In the brainstem, COX 2-ir neurons were observed in the dorsal raphe nucleus, the nucleus of the brachium of the inferior colliculus, and in the region of the subcoeruleus. The distribution of COX 2-ir neurons in the CNS suggests that COX 2 may be involved in processing and integration of visceral and special sensory input and in elaboration of the autonomic, endocrine, and behavioral responses.

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

“…Qualitatively, a greater number of neurons were positively stained for COX-2 in the young brain than seen in the aged brain however, the less number of neurons appeared to show a greater staining intensity with age (Fig 4A,C). While previous studies report a prominent localization of COX-2 in the rat cortex and hippocampus [12,28], the current study showed that staining was also evident in the cerebellum of the non-human primate. Purkinje neurons of the cerebellum were immunopositive for COX-2 with staining localized to the cytoplasm of the cell body and extending into the processes.…”

Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

“…In addition, recent investigations have found a potentiation of excitotoxicity in transgenic mice overexpressing neuronal COX-2 [37] and a significant reduction in ischemic brain injury in COX-2-deficient mice [36,62]. COX-2 expression by itself does not lead to neuronal death since a variety of healthy neuronal populations throughout the CNS express COX-2 mRNA and protein under normal conditions [5,77] and COX-2 expression can be experimentally induced without causing neuronal death [56]. In the study of Planas et al [56], they found the same level of COX-2 induction in response to both 10 min (mild enough not to cause inflammation or cell death) and 1 h of stroke (which leads to brain infarct), suggesting that COX-2 would only mediate neuronal injury in the context of an inflammatory response.…”

The pharmacological properties and clinical use of valdecoxib, a new cyclo‐oxygenase‐2‐selective inhibitor

“…58,59 These findings raise the question of whether the inhibition of COX-2 in the central nervous system with 'coxibs' and NSAIDs may be responsible for the common drug-related central nervous system disorders, such as dizziness and headache, as well as the less common reactions, such as somnolence, vertigo and paraesthesia.…”